This invention relates to chromatographic separations, particularly industrial scale chromatographic separations made using an ion-exchange resin as the separating medium.
Chromatographic separations of various substances can be accomplished using ion exchange resins as the stationary phase. Such processes use anion or cation exchange resins to separate mixtures of organic compounds, mixtures of organic compounds and salts, mixtures of acids and salts, and salt mixtures. Of particular commercial importance is the separation of fructose from glucose and oligosaccharides in the production of high fructose corn syrup (HFCS). In this process, mixtures of glucose and fructose are passed through one or more columns of a strong acid type ion exchange resin, most typically in the calcium form. The passage of the fructose through the column is retarded relative to that of the glucose, so there can be obtained separate product streams containing high proportions of fructose and glucose. The high fructose-containing stream is then used as a sweetener for many foodstuffs, such as soft drinks. This process is illustrated by Welstein and Sauer in "Separation of Glucose and Fructose: Effects of Resin Characteristics on Separation", in Ion Exchange Technology, Naden and Streat, eds. Society of Chemical Industry, London, pp. 466-471, incorporated herein by reference.
The ion-exchange resin used in such chromatographic separations is typically a plurality of crosslinked copolymer particles which contain anion or cation-exchange groups. Previous to this invention, this resin was a gel-type resin wherein the copolymer is prepared by a one-step suspension polymerization process using a low to moderate level of cross-linker and little or no inert diluent. As used hereinafter, the term "conventional one-step process" refers to a process like that described in U.S. Pat. No. 3,044,905, the teachings of which are incorporated herein by reference.
Although good chromatographic separations can be achieved with the above-described gel resins, improvements which result in a faster, more efficient and/or higher yield operation of the column are always desirable. Thus, it has been attempted to modify the ion-exchange resin to improve its kinetics. All other things being equal, faster exchange kinetics would provide several decided advantages. For example, at a given purity and yield, faster exchange kinetics would permit the column to be operated more rapidly (i.e., use higher feed rates). Alternatively, higher yields and/or product purities could be obtained at equivalent operating conditions if the resin had improved kinetics. Another advantage is that less desorbing solvent could be used, thereby reducing the expense of separating same from the product. Faster kinetics would also allow the use of larger resin particles, which permits a faster feed rate and/or higher feed concentration, thereby obtaining equal or better yield and purity without increasing pressure drop across the bed. A resin having faster kinetics would also permit the feed concentration to be increased in order to obtain a faster production rate.
Besides kinetics, another important parameter of a resin is its flow characteristics, i.e., the ease with which a liquid flows through a bed of the resin. It is desirable that the mobile phase move rapidly through the resin at low pressures. The equipment normally used in commercial chromatographic separation cannot withstand high pressures, so the flow rate cannot be greatly increased merely by increasing the pressure on the mobile phase.
It has been found that most modifications which improve the kinetics of conventional ion-exchange resins simultaneously diminish their flow characteristics. It is known that the kinetics of the resin can be improved by decreasing the particle size or increasing the water retention capacity. Unfortunately, both of these modifications diminish the flow characteristics of the resin so that, at a given pressure, a lower rate of sure, a lower rate of flow of the mobile phase is obtained. In practice, the benefit of the improved kinetics is at least offset by the undesirable worsening of the flow characteristics.
Accordingly, it would be desirable to provide a process for the chromatographic separation of a mixture of two or more materials, using an ion-exchange resin as the stationary phase, wherein a faster, more efficient or higher purity separation is achieved.